在ADORA2A驱动的林合成引发了神经内分泌前列腺癌和肺癌中的表观遗传重编程
Na Jing1,2, Kai Zhang1, Xinyu Chen1
1State Key Laboratory of Systems Medicine for Cancer, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine and School of Biomedical Engineering, and.
The Journal of clinical investigation
|December 15, 2023
概括
向治疗由于癌细胞可塑性而失败. 这项研究确定ADORA2A是神经内分泌分化的关键驱动力,为前列腺癌和肺癌提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 癌细胞谱系的可塑性有助于治疗抵抗.
- 确定这种可塑性的驱动因素对于开发有效的治疗方法至关重要.
研究的目的:
- 识别调节癌细胞谱系可塑性的新型药物标,特别是神经内分泌分化.
主要方法:
- 研究了G蛋白结合受体ADORA2A在癌细胞谱系可塑性中的作用.
- 利用了基因工程小鼠模型和ADORA2A.的药理阻断.
- 分析了涉及的信号通路,包括プロ林代谢和表观遗传修饰.
主要成果:
- 在前列腺癌和肺癌中,ADORA2A在神经内分泌分化过程中受到上调.
- 通过ERK/MYC/PYCR级联,ADORA2A激活改变了普林代谢,促进了神经内分泌系.
- 废除ADORA2A可以抑制神经内分泌癌症的进展,并防止表型转变.
- 药理上抑制ADORA2A可以抑制神经内分泌癌症的生长.
结论:
- ADORA2A 是神经内分泌分化的关键调节者,也是潜在的治疗标.
- 向ADORA2A可能通过调节表观遗传重编程来克服神经内分泌前列腺和肺癌中的抵抗.
相关概念视频
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K
Cancer-Critical Genes I: Proto-oncogenes
8.9K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.9K


